The word ‘essential’ is used in nutrition to describe a nutrient that we cannot synthesise ourselves but must obtain via our food intake. Zinc is an essential trace element, or micronutrient.
However, we only discovered that zinc was essential for plants in 1869, for experimental animals in 1932, and for humans in 1961.
Zinc is involved in more than 300 different enzyme activities related to a variety of important cellular activities. This extensive requirement for zinc strongly suggests that a deficiency in this mineral will result in a variety of impairments across many metabolic functions.
Research has shown that the central nervous system (CNS), along with epidermal, gastrointestinal, immune, reproductive, and skeletal systems are all affected by zinc deficiency.
There is increasing evidence that many factors including dietary, hereditary, and environmental factors can adversely affect zinc balance/homeostasis and could have a profound effect on human health and behaviour.
Within the brain, 80 to 90% of all zinc is protein bound. The remaining zinc is localised within synaptic vesicles of nerve terminals and is referred to as vesicular zinc.
So, What Exactly Does Zinc Do?
Zinc works with protein and can serve as a catalyst [causes or accelerates a reaction], in a structural [arrangement of components] capacity, or as a regulatory agent [controls or maintains rate or speed].
• In its role as a catalyst, it’s involved - along with other nutrients - in the process of converting amino acids (proteins) into neurotransmitters, like serotonin and dopamine, and stress hormones (adrenalin), and reproductive hormones.
• Zinc is also critical for thyroid hormone synthesis as well as insulin and leptin synthesis.
• In its structural role, zinc is involved in maintaining the structure and therefore the integrity and the functionality of cell membranes.
• In its regulatory role, zinc is involved with cellular growth and differentiation, which includes gene expression and transcription (DNA (Deoxyribonucleic Acid)
and RNA (ribonucleic acid)) activities and apoptosis (programmed cell death.)
• Zinc also forms part of what are called ‘zinc finger proteins’ that act as DNA binding transcription factors.
• Zinc's role in skin health and wound healing is multifaceted as it’s required for collagen and protein synthesis, along with cell proliferation, and immune function, which are all essential for tissue regeneration and repair.
• In addition, all proliferating cells, including inflammatory and epithelial cells, and fibroblasts, require zinc.
Optimal CNS Development and Functioning Needs Zinc
There are three different stages to be considered when examining the function of zinc in brain pathology:
1. CNS development in embryonic and early postnatal stages
2. Functioning related to the developing brain
3. Neurodegenerative disorders of ageing.
Adverse neurological effects during early brain development stages appear to be permanent, showing little or no improvement from zinc replacement therapy.
The mechanism by which zinc deficiency causes abnormal brain formation and development has been attributed to impaired cell division during embryonic development.
Because zinc plays a critical role in replication transcription and translation, compromising status may lead to abnormal cell cycle regulation and organ development.
Although its precise role has yet to be defined at the neuronal synapse, vesicular zinc appears to be released into the synapse during neural activity, where it may serve to modulate neurotransmitter receptors, including pre- and postsynaptic glutamate receptors.
Zinc may also serve a more global but equally vital role as an antioxidant in the brain. This may be particularly relevant to ageing and its association with increased oxidative stress and diminished antioxidant defences.
The other mechanisms by which zinc deficiency impacts the CNS in these three stages result in clinical pathologies that are probably distinctly different, as discussed next.
Zinc Deficiency
Next to iron, zinc is the most common mineral found in the body and is found in every cell. Zinc and copper work in relation to each other, and too much zinc may lead to a copper deficiency.
A deficiency in zinc, whether at the catalytic, structural, or regulatory level, will impact a variety of behavioural and cognitive functions.
Zinc deficiency has been implicated in several neurological disorders, such as Alzheimer’s, Parkinson’s, and Lou Garricks disease, as well as other behavioural abnormalities.
Zinc deficiency has been noted in some food disorders, such as anorexia, because zinc is involved in serotonin synthesis, which is required to moderate appetite, and zinc is involved in taste receptors on our tongue.
Zinc deficiency may therefore play a role in the onset and maintenance of anorexia.
Symptoms of zinc deficiency mirror this eating disorder, and include amenorrhea, body dysmorphia, decreased appetite, decreased and altered sense of taste and smell, depression, insomnia, nausea while eating, poor sleep, and weight loss.
Stress may also lead to a deficiency in zinc, due to its role in synthesising stress hormones. The more stress hormones are required, the more zinc is required, and the less is available to synthesise serotonin and melatonin, as well as other neurotransmitters.
A deficiency in zinc may therefore be linked to an inability to bounce back from stress, as well as sleep and appetite challenges.
Zinc deficiency induced a loss in blood brain barrier (BBB) integrity in animal studies. Lack of BBB integrity increases risk of brain inflammation which leads to increased risk of neuropathologies.
Supplementation of zinc and a macro nutrient mixture has been found to improve tests of memory, reasoning, and psychomotor functioning in comparison with subjects given the micronutrient mixture only. This suggests that micro and macro nutrients work together to optimise cognitive function.
Zinc deficiency may also increase lethargy, due to its role in cellular energy production.
Changes in Brain Zinc Concentration Across Time
As stated, zinc is essential for brain development. A deficiency in this nutrient can lead to a variety of malformations during embryogenesis and can lead to behavioural deficits in both animals and humans.
However, there are changes in distribution and concentration of zinc during postnatal growth, with a gradual rise in zinc content in different brain regions. This may reflect a particular functional role of zinc in each brain region across developmental phases.
The gradual increase in zinc content in the cerebral cortex and the hippocampus may be indicative of the role of zinc in neurotransmission, memory and learning, processes associated with the development and maturation of cognitive circuits in these brain regions.
These regions are also associated with emotion, leading researchers to speculate that changes in zinc concentration coupled with a deficiency could lead to challenges related to regulating emotions.
These changes in zinc concentration across the brain may be related to deficiencies among the elderly as the brain ages, explaining the relationship between noted zinc deficiencies in elderly populations and age-associated risk of dementias and other neuropathologies.
Zinc and Gut Health
Zinc homeostasis within the brain is dependent not only on zinc absorption and excretion in the gastrointestinal (GR) track, but also on regulatory mechanisms that control zinc transport through the BBB system.
The BBB system is critical to brain tissue, regulating brain zinc turnover in a manner considerably slower than in peripheral tissues.
Although brain zinc levels are usually not affected by dietary zinc, some neuromotor and cognitive dysfunction is associated with zinc deficiency which argues against the view that brain zinc levels are not affected by dietary zinc.
In animal models, dietary zinc is absorbed and transported through intestinal epithelial cells into the blood where most is bound and transported by albumin.
However, many factors influence its absorption, such as competition with other metal species, such as iron and copper, and the presence of dietary zinc binding ligaments that may facilitate or inhibit zinc absorption.
Zinc and iron compete for absorption within the digestive system. This means that when both nutrients are consumed at the same time, at levels commonly used in dietary supplements, there is evidence to suggest that an excess of iron inhibits the absorption of zinc, and that excess zinc inhibits iron uptake.
These nutrients should not be consumed without a blood test that shows a deficiency, and if required, should not be consumed at the same time.
It’s also important to keep track of copper status as too much zinc can lead to a copper deficiency as it can reduce the amount of copper absorbed.
However, not only is zinc absorbed via the GR, an oversupply or zinc deficiency will compromise the health of the gut lining and shift the gut microbiome.
This will lead to digestive challenges coupled with a body and brain inflammatory response.
Food Sources of Zinc
Oysters are the richest source of zinc, as well as shrimp, crab, and other shellfish. However, due to the toxicity present in oceans today, these foods may not be the best sources of zinc if overall brain health is the goal.
Red meats, poultry, ricotta, Swiss and gouda cheeses, are all good sources too.
Less easily absorbed plant sources of zinc include legumes, such as lima beans, black-eyed peas, pinto beans, soybeans, and peanuts, along with whole grains, miso, tofu, greens, mushrooms, green beans, tahini (sesame seeds), along with pumpkin and sunflower seeds.
The most bioavailable supplemental forms of zinc are zinc picolinate, citrate, acetate, glycerate and zinc monomethionine.
In conclusion, zinc is not only critical from a structural perspective in relation to brain development, it also plays a significant role in behavioural and cognitive aspects of brain function via its catalytic and regulatory roles.
The body and brain requirement for zinc increases as stress increase. In the presence of chronic stress it is therefore imperative to be tested for a deficiency to prevent sub-optimal cognitive functioning.
The many and varied roles of zinc in the body and brain, and the numerous pathologies associated with a deficiency in this nutrient, point to its importance as an essential mineral that is critical to brain function.
References
Cope, E.C, et al. (2010) Role of zinc in the development and treatment of mood disorders. Current Opin Clin Nutr Metab Care; 13(6):685-9.
Du, K. et al. (2017) Decreased circulating Zinc levels in Parkinson’s disease: a meta-analysis study. Sci Rep; 7: 3902.
Frederickson, C. J. et al. (2000) Importance of Zinc in the Central Nervous System: The Zinc-Containing Neuron. The Journal of Nutrition; 130(5): 1471S–1483S.
Hambidge, M. (2000) Human Zinc Deficiency in Zinc and Health: Current Status and Future Directions. American Society for Nutritional Sciences. 1344S – 1349S.
Humphries, L. et al. (1989). Zinc deficiency and eating disorders. The Journal of Clinical Psychiatry, 50(12), 456–459.
Huskisson E. et al. (2007). The influence of micronutrients on cognitive function and performance. J Int Med Res; 35(1): 1-19.
Lieberman, H. R. et al. (2005) Human Nutritional Neuroscience: Fundamental. Issues. Nutritional Neuroscience. Ed: Lieberman, H. R., Kanarek, R. B. and Prasad, C. New Orleans, USA: Taylor and Francis.
Maret, W. et al. (2008) Possible roles of zinc nutriture in the fetal origins of disease. Exp. Gerontol; 43, 378–381.
McCabe, D, et al. (2020) Women's Health Reports; 241-251.
McCabe, D. et al. (2017) The impact of essential fatty acid, B vitamins, vitamin C, magnesium and zinc supplementation on stress levels in women: a systematic review, JBI Database of Systematic Reviews and Implementation Reports; 15 (2): 402-453.
McCabe, D. (2016) Feed Your Brain. 7 Steps to a Lighter, Brighter You! Sydney, Australia: Exisle Publishing.
Roohani N. et al. (2013) Zinc and its importance for human health: An integrative review. J Res Med Sci;18:144‐57.
Saper R. et al. (2008) Zinc: An essential micronutrient. Am Fam Phys;79(9).
Shay N.F. et al. (2000) Neurobiology of zinc-influenced eating behavior. J Nutr; 130(5S Suppl):1493S-9S.
Song Y. et al. (2009) Zinc deficiency affects DNA damage, oxidative stress, antioxidant defences, and DNA repair in rats. J Nutr;139(9):1626-1631.
Szewczyk B. (2013) Zinc homeostasis and neurodegenerative disorders. Front. Aging Neurosci; 5:33.
Thomas D. E. (2007) The mineral depletion of foods available to us as a nation (1940-2002) – A review of the 6th edition of McCance and Widdowson. Nutr Health; 19(1-2): 21-55.
Watts M, editor. (2009) Nutrition and Mental Health – a handbook. Brighton, UK: Pavilion Pub.